Donor Desmopressin Treatment Does Not Affect Transplant Outcome in the Fischer to Lewis Rat Renal Transplant Model.

Abstract

OBJECTIVES:

Retrospective studies suggest that donor desmopressin (DDAVP) treatment improves renal transplant outcome. The present study tests the hypothesis that desmopressin neutralizes the graft's endothelium from proinflammatory angiopoietin 2 containing Weibel-Palade bodies in the donor, resulting in reduced Weibel-Palade body release at the time of reperfusion in the recipient.

MATERIALS AND METHODS:

Using rat models, we examined the influence of desmopressin treatment on the expression of vasopressin 2 receptors and adhesion molecules in brain-dead donors, with renal function examined in allogeneic recipients. The influence of desmopressin on the expression of adhesion molecules also was tested in vitro.

RESULTS:

Vasopressin 2 receptors were restricted to collecting ducts and distal tubules and only scarcely found in the renal vasculature. Vasopressin 2 receptor expression was down-regulated in brain-dead rats by desmopressin. Renal expression of vascular cellular adhesion molecule 1 and intercellular adhesion molecule 1 were significantly reduced in these rats. In contrast, angiopoietin 2 did not influence the expression of adhesion molecules in in vitro cultured endothelial cells after tumor necrosis factor ? stimulation. Donor desmopressin treatment improved neither renal function nor histology in allogeneic renal transplant recipients.

CONCLUSIONS:

Our data do not support the hypothesis that the clinically observed salutary effect of desmopressin is mediated by depletion of Weibel-Palade bodies in renal allografts.

• Authors: Heiko M Mundt, Simone Höger, Rüdiger Waldherr, Peter Schnuelle, Bernhard K Krämer, Benito A Yard, Uwe Göttmann, Urs Benck
• Journal: Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation (Exp Clin Transplant) Vol. 14 Issue 3 Pg. 299-306 (06 2016) ISSN: 2146-8427 [Electronic] Turkey
• PMID: 27221721 (Publication Type: Journal Article)

Chemical References

• Angiopoietin-2
• ICAM1 protein, rat
• Receptors, Vasopressin
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Deamino Arginine Vasopressin

Topics

• Angiopoietin-2 (pharmacology)
• Animals
• Cells, Cultured
• Cold Ischemia (adverse effects)
• Deamino Arginine Vasopressin (pharmacology)
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, metabolism, pathology)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism, pathology)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Kidney (drug effects, metabolism, pathology)
• Kidney Transplantation (adverse effects)
• Male
• Models, Animal
• Rats, Inbred F344
• Rats, Inbred Lew
• Receptors, Vasopressin (agonists, metabolism)
• Reperfusion Injury (metabolism, pathology, prevention & control)
• Time Factors
• Transplantation, Homologous
• Tumor Necrosis Factor-alpha (pharmacology)
• Vascular Cell Adhesion Molecule-1 (metabolism)
• Warm Ischemia (adverse effects)
• Weibel-Palade Bodies (drug effects, metabolism, pathology)